Gadrey Shrirang M, Mohanty Piyus, Haughey Sean P, Jacobsen Beck A, Dubester Kira J, Webb Katherine M, Kowalski Rebecca L, Dreicer Jessica J, Andris Robert T, Clark Matthew T, Moore Christopher C, Holder Andre, Kamaleswaran Rishi, Ratcliffe Sarah J, Moorman J Randall
University of Virginia School of Medicine, Charlottesville; and Emory University, Atlanta, USA.
medRxiv. 2022 Jun 16:2022.06.14.22276166. doi: 10.1101/2022.06.14.22276166.
Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously, but occult hypoxemia can occur in Black patients because the technique is affected by skin color. Oxygen dissociation curves allow non-invasive estimation of P/F ratios (ePFR) but this approach remains unproven.
Can ePFRs measure overt and occult hypoxemia?
We retrospectively studied COVID-19 hospital encounters (n=5319) at two academic centers (University of Virginia [UVA] and Emory University). We measured primary outcomes (death or ICU transfer within 24 hours), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score (NEWS) and Sepsis-3). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AOR) and area under receiver operating characteristics curves (AUROC). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test.
Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; p<0.01) with better discrimination (AUROC: 0.76 [UVA]; 0.71 [Emory]) than NEWS (AUROC: 0.70 [UVA]; 0.70 [Emory]) or Sepsis-3 (AUROC: 0.68 [UVA]; 0.65 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites]; p<0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA]; 1.2 [Emory], p<0.01).
The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models like NEWS and Sepsis-3. By accounting for biased oximetry as well as clinicians’ real-time responses to it (supplemental oxygen adjustment), ePFRs may enable statistical modelling of racial disparities in outcomes attributable to occult hypoxemia.
进行性低氧血症是新冠病毒病（COVID-19）病情恶化的主要模式。在低氧血症的各项指标中，动脉血氧分压与吸入氧分数之比（P/F比值）具有最佳的结构效度，但由于需要采集动脉血样，其可用性较差。脉搏血氧饱和度仪可连续报告氧合情况，但由于该技术受肤色影响，黑人患者可能会出现隐匿性低氧血症。氧解离曲线可用于无创估计P/F比值（ePFR），但这种方法尚未得到验证。
ePFR能否检测显性和隐匿性低氧血症？
我们对两个学术中心（弗吉尼亚大学[UVA]和埃默里大学）收治的COVID-19患者（n = 5319）进行了回顾性研究。我们测量了主要结局（24小时内死亡或转入重症监护病房）、ePFR、传统低氧血症指标、基线预测因素（年龄、性别、种族、合并症）以及急性预测因素（国家早期预警评分（NEWS）和脓毒症-3）。我们每隔15分钟更新一次预测因素。我们使用调整后的优势比（AOR）和受试者工作特征曲线下面积（AUROC）评估预测效度。我们使用柯尔莫哥洛夫-斯米尔诺夫（K-S）双样本检验对经验累积分布中的种族差异（黑人与非黑人）进行了量化。
显性低氧血症（ePFR低）可预测不良结局（ePFR下降100分时的AOR：UVA为2.7；埃默里大学为1.7；p<0.01），其判别能力（AUROC：UVA为0.76；埃默里大学为0.71）优于NEWS（AUROC：UVA为0.70；埃默里大学为0.70）或脓毒症-3（AUROC：UVA为0.68；埃默里大学为0.65）。我们发现了与隐匿性低氧血症一致的种族差异。黑人患者的表观氧合情况较好（K-S距离：两个研究地点均为0.17；p<0.01），但在ePFR相当的情况下，其结局比其他患者更差（AOR：UVA为2.2；埃默里大学为1.2，p<0.01）。
ePFR是显性低氧血症的有效指标。在COVID-19中，它可能优于NEWS和脓毒症-3等多器官功能障碍模型。通过考虑脉搏血氧饱和度测量的偏差以及临床医生对其的实时反应（补充氧气调整），ePFR可能能够对隐匿性低氧血症所致结局的种族差异进行统计建模。
